Objective: To demonstrate a role for vitamin E in cell culture and to elucidate the responses of normal and transformed cells to the vitamin under different conditions of growth. Approach: It is known that in animals, the requirement for vitamin E is linked to the amount of polyunsaturated fatty acids in the diet. It is also known that in standard tissue culture media, cells can grow without the vitamin. Our assumption has been that cells can be induced to demonstrate their requirement for the vitamin by altering the medium so that the cell's metabolism approaches that seen with tissues in vivo. Cells in culture normally rely heavily on glycolysis for their energy supply. If the cells could be forced to use a more aerobic metabolism utilizing the Krebs' cycle and the electron transport scheme, then a requirement might be demonstrated. In addition, if the cell might be forced to incorporate higher levels of PUFA, a requirement for vitamin E could be shown. This could be accomplished by removing lipids from the media by extraction of the serum with acetone. It should then be possible to demonstrate the interaction of vitamin E, PUFA, and cholesterol at the membrane level. Inasmuch as cancer cells may require glycolytic mechanisms and may have an altered lipid composition in the membrane, a comparison with normal cells will be made.